Malignant transformation of epidermoid cysts (ECs) to squamous cell carcinomas (SCCs) in the CNS is exceedingly rare and has only been described in intracranial ECs. In this article, the authors describe a 53-year-old man with a history of a previously resected T3–4 EC, who presented with a 2-month history of progressively worsening weakness in the left side of his body. Magnetic resonance imaging revealed an enhancing mass in the T3–4 region, the exact location of the previous cyst. The mass was resected in gross-total fashion, and pathological analysis revealed an SCC. Postoperatively, the patient regained full strength in his lower extremities. After the resection, he received radiotherapy administered at an isodose of 50 Gy. To the authors' knowledge, this is the first reported case of malignant transformation of an intramedullary spinal EC in the literature.